RetroRules: a database of reaction rules for engineering biology

Area of Science:

• Metabolic Engineering
• Synthetic Biology
• Computational Chemistry

Background:

• Reaction rules are crucial for retrosynthesis and pathway discovery in metabolic engineering.
• Enzyme promiscuity is increasingly exploited in synthetic biology and systems biology.
• Existing reaction rule databases lack stereochemistry awareness and diverse specificity levels.

Purpose of the Study:

• To provide a comprehensive, stereochemistry-aware database of reaction rules.
• To represent reaction rules at multiple levels of specificity.
• To expand the prediction of de novo reactions for promiscuous enzymes.

Main Methods:

• Extracted >400,000 reaction rules from public databases.
• Expressed rules in the SMARTS (SMIRKS) format.
• Augmented rules with representations at different atomic environment specificities.

Main Results:

• Developed RetroRules, a database of >400,000 stereochemistry-aware reaction rules.
• Rules are available in SMARTS format with varying specificity.
• The database facilitates the enumeration of biosynthetic routes.

Conclusions:

• RetroRules significantly enhances de novo pathway discovery and the study of enzyme promiscuity.
• The stereochemistry-aware and multi-specificity approach expands chemical diversity prediction.
• This resource is vital for advancing metabolic engineering and synthetic biology applications.